1646 Br J Ophthalmol: first published as 10.1136/bjo.2005.072546 on 18 November 2005. Downloaded from PERSPECTIVE Hypertensive retinopathy revisited: some answers, more questions A Grosso, F Veglio, M Porta, F M Grignolo, T Y Wong ............................................................................................................................... Br J Ophthalmol 2005;89:1646–1654. doi: 10.1136/bjo.2005.072546 Hypertension is associated with cardiovascular risk and Guidelines (BHS IV)15 consider retinopathy as target organ damage, although again only for systemic target organ damage. Retinopathy is considered grades III and IV. one of the indicators of target organ damage. This review There are a number of considerations that may focuses on recent studies on hypertensive retinopathy and militate against systematic retinal examination in patients with hypertension. These include their implications for clinical care. Early recognition of vague definitions and heterogeneous classifica- hypertensive retinopathy signs remains an important step tions of hypertensive retinopathy, making sever- in the risk stratification of hypertensive patients. ity staging a largely arbitrary process, as well as the lack of well defined prognostic value for ........................................................................... either systemic outcomes or visual impairment. ypertension is a worldwide problem that EPIDEMIOLOGY affects up to 50 million people in the Several recent studies have shown that retinal United States and approximately one microvascular changes can be reliably documen- H 16–23 billion worldwide, and is the single most ted by retinal photographs. In general, repro- important modifiable risk factor for stroke.1–3 ducibility from photographs has been found to Even milder degrees of blood pressure elevation be excellent for well defined retinopathy signs pose increased risk for cardiovascular events. (kappa values ranged from 0.80 to 0.99 for Unfortunately, hypertension awareness, treat- microaneurysms and retinal haemorrhages) and ment, and control remain less than optimal.45 fair to moderate for other more subtle retinal Hypertension acts as a silent killer many years arteriolar lesions (0.40–0.79 for arteriolar nar- before overt end organ damage is clinically rowing and arteriovenous nicking).24 apparent. Hence, the importance of refining risk Furthermore, these studies suggest that gen- stratification strategies to ensure reliable detec- eralised arteriolar narrowing could be estimated tion of hypertension related end organ damage from an assessment of retinal vessel diameters before it becomes symptomatic. on photographs by use of imaging software. The The retina provides a window to study the development of specific software packages have human circulation. Retinal arterioles can be made it possible to objectively measure the http://bjo.bmj.com/ visualised easily and non-invasively and share arteriole to venule ratio (AVR) in selected similar anatomical and physiological properties standardised portions of the retina.16 17 This with cerebral and coronary microcirculation.6–10 technique appears to have substantial reprodu- cibility (intraclass correlation coefficient ranged 17 20–23 DETECTION OF HYPERTENSIVE from 0.80–0.99). RETINOPATHY On the basis of retinal photography, retinal Poorly controlled systemic hypertension causes microvascular signs are common in adults on September 26, 2021 by guest. Protected copyright. damage to the retinal microcirculation, so that 40 years of age and older, even in those without recognition of hypertensive retinopathy may be history of diabetes and hypertension. Both important in cardiovascular risk stratification of prevalence and incidence of between 2–15% have hypertensive patients.11 However, there is no been reported for various retinal microvascular 19–25 widely accepted classification or definition of lesions. hypertensive retinopathy. Various international management guidelines are not consistent in this WHAT RETINAL SIGNS ARE CLINICALLY respect. For example, the risk stratification table USEFUL TO CLINICIANS FOR RISK See end of article for (table 1) from the European Society of ASSESSMENT? authors’ affiliations Hypertension-European Society of Cardiology Data from population based studies indicate that ....................... Guidelines (ESH-ESC 2003)12 indicates that certain signs of hypertensive retinopathy (table 3) Correspondence to: hypertensive retinopathy grades III and IV (as are associated with increased cardiovascular risk, Andrea Grosso, MD, defined from table 2) are associated clinical Department of Clinical conditions, while the Joint National Committee Physiopathology, Abbreviations: ABPM, ambulatory blood pressure Ophthalmology Section, on Prevention, Detection, Evaluation, and monitoring; AION, anterior ischaemic optic neuropathy; Turin University, Via Treatment of High Blood Pressure (JNC VII) in AMD, age related maculopathy; AVR, arteriole to venule Juvarra, 19, 10122 Turin, the United States indicates generically retino- ratio; BP, blood pressure; CHD, coronary heart disease; Italy; [email protected] pathy (without mention of grade) as target organ CVD, cardiovascular disease; IMT, intima-media 13 thickness; LVH, left ventricular hypertrophy; MRI, Accepted for publication damage. Additionally, the WHO International magnetic resonance imaging; RAO, retinal arterial 1 July 2005 Society of Hypertension (WHO-ISH) 2003 state- occlusion; RVO, retinal vein occlusion; WCH, white coat ....................... ment14 and the British Hypertension Society 2004 hypertension www.bjophthalmol.com Hypertensive retinopathy 1647 Br J Ophthalmol: first published as 10.1136/bjo.2005.072546 on 18 November 2005. Downloaded from Table 1 Different prognostic classification of hypertensive retinopathy, according to the European Society of Hypertension-European Society of Cardiology (ESH-ESC) 2003 Guidelines, the JNC 7 Report, the British Hypertension Society (BHS) IV 2004 Guidelines, and the World Health Organization–International Society of Hypertension (WHO/ISH) 2003 statement on diagnosis and treatment of hypertension WHO/ISH 2003 statement14 and ESH-ESC 2003 guidelines12 JNC 7 report 200313 BHS IV 2004 guidelines15 Associated clinical conditions Target organ damage Target organ damage Advanced retinopathy: haemorrhages or Retinopathy Hypertensive retinopathy grade III exudates, papilloedema or IV independently of other risk factors.23 26–28 Generalised and focal retinal arteriolar narrowing has been shown to predict the risk of hypertension in normotensive people.29–31 Generalised arteriolar narrowing (fig 1), focal arteriolar narrowing, arteriovenous nicking (fig 2), opacity (copper wire) of arteriolar wall, or a combination of these (mild grade of retinopathy) have been associated with a mild increase (odds ratio greater than 1 but less than 2) of incident clinical stroke, coronary heart disease, and death. The Atherosclerosis Risk in Communities Study showed that generalised arter- iolar narrowing of the retinal arterioles was associated with subsequent coronary heart disease in women (relative risk, 2.2; 95 confidence interval 1.0 to 4.6) but not in men (relative 32 Figure 1 Mild hypertensive retinopathy. Photograph shows generalised risk, 1.1; 95 confidence interval 0.7 to 1.8). Furthermore, in retinal arteriolar narrowing. the ARIC Study generalised arteriolar narrowing of the retinal arterioles was found to be independently associated with increased risk for type 2 diabetes (odds ratio, 1.71; 95 confidence interval 1.13 to 2.57).33 Haemorrhages (blot, dot, or flame shaped), microaneur- ysms, cottonwool spots, hard exudates (fig 3), or a combina- tion of these signs (moderate grade of retinopathy) are more strongly associated (odds ratio of 2 or greater) with risk of incident clinical stroke,34 presence and severity of magnetic resonance imaging (MRI) defined cerebral white matter lesions and cerebral atrophy defined on MRI,35 reduced cognitive performance on standardised neuropsychological http://bjo.bmj.com/ tests,36 37 and death from cardiovascular causes.28 The ARIC Study reported that people with microaneurysms, retinal haemorrhages, and soft exudates were two to three times Figure 2 Mild hypertensive retinopathy. Photograph shows more likely to develop an incident clinical stroke over 3 years arteriovenous nicking (white arrow). than people without these retinal lesions, independently of blood pressure, diabetes, cigarette smoking, elevated lipid levels, and other risk factors.34 Furthermore, there was a among participants who had white matter lesions only, the multiplicative interaction between the presence of retinal relative risk of stroke was 3.4 (confidence interval, 1.5 to on September 26, 2021 by guest. Protected copyright. microvascular changes and white matter lesions on the risk 7.7).35 of stroke. The 5 year relative risk of stroke among partici- In a nested case-control study in patients with age related pants who had both hypertensive retinopathy and cerebral eye diseases in Wisconsin (the Beaver Dam Eye Study) the lesions on MRI, compared with those who had neither of presence of retinal microaneurysms, retinal haemorrhages, these findings, was 18.1 (confidence interval, 5.9 to 55.4); and retinal arteriolar narrowing was associated with a high Table 2 The Keith, Wagener, and Barker117 hypertensive retinopathy classification (grade I–IV), based on the level of severity of the retinal findings Grade Classification Symptoms Grade I (mild hypertension)